Bromine → N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-fluorophenyl}-2-chloro-3-(1-cyano-1-methylethyl)benzamide

HRID 2190478Notes

Reaction equation

HRID 2190478 reaction equation
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:34]=[CH:33][C:9]([O:10][C:11]2[CH:12]=[C:13]([NH:18][C:19](=[O:32])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[C:21]=3[Cl:31])[CH:14]=[CH:15][C:16]=2[F:17])=[CH:8][CH:7]=1.BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:7]2[CH:8]=[C:9]([O:10][C:11]3[CH:12]=[C:13]([NH:18][C:19](=[O:32])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:27])[CH3:28])[C:21]=4[Cl:31])[CH:14]=[CH:15][C:16]=3[F:17])[CH:33]=[CH:34][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 67312572HCID 67312572, compound

Product 1

HCID 86655406N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-fluorophenyl}-2-chloro-3-(1-cyano-1-methylethyl)benzamideYield 43%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

To a solution of potassium thiocyanate (1.65 g, 17.0 mmol) in acetic acid (15 mL) was added a solution of N-[3-(4-aminophenoxy)-4-fluorophenyl]-2-chloro-3-(1-cyano-1-methylethyl)benzamide (1.75 g, 4.13 mmol) in acetic acid (5 mL), and the mixture was stirred at room temperature for 15 min. To the obtained solution was added dropwise a solution of bromine (726 mg, 4.54 mmol) in acetic acid (15 mL) at room temperature over 30 min or longer. After the completion of the dropwise addition, the mixture was stirred at room temperature for 4 hr. The resulting yellow solid was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL) and ethyl acetate (200 mL), and basified with 2N aqueous sodium hydroxide solution. The aqueous layer was separated, and the organic layer was washed with saturated aqueous ammonium chloride solution (200 mL) and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (854 mg, 43%) as a yellow amorphous substance. The obtained compound was used in the next reaction without a further purification.

Workup

  1. additionAfter the completion of the dropwise addition
  2. stirringthe mixture was stirred at room temperature for 4 hr
  3. filtrationThe resulting yellow solid was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in tetrahydrofuran (100 mL)
  6. customThe aqueous layer was separated
  7. washthe organic layer was washed with saturated aqueous ammonium chloride solution (200 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe insoluble material was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-5cbbddb2d1954cad8ffaa14a4591e53d
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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